【摘要】 目的 对甘草次酸（GA）介导的马钱子碱自组装纳米粒甘草次酸-聚乙二醇-二硫代二丙酸-单硬脂酸甘油酯（B-GPSG-NPs）、马钱子碱（B）、马钱子碱自组装纳米粒聚乙二醇-二硫代二丙酸-单硬脂酸甘油酯（B-PSG-NPs）进行药动学比较研究。方法 采用HPLC法测定马钱子碱在血浆中的含量。18只健康大鼠，雌雄各半，随机分成马钱子溶液组，B-GPSG-NPs溶液组以及B-PSG-NPs溶液组，经尾静脉注射后在不同时间点大鼠眼眶取血，分别于给药后的不用时间点（10、30、60、90、120、150、180、210、240、300、420、600 min）进行眼底静脉丛毛细管取血，HPLC含量测定后采用DAS 2.0软件对药时数据进行方程拟合，得出药动学参数，进行药动学评价。结果 B-GPSG-NPs溶液组中药物的t_l/2α、t_1/2β分别是马钱子碱溶液组中药物的3.11、2.18倍，AUC值是马钱子碱溶液组中药物的3.7倍，血浆清除率是马钱子碱溶液组的0.31倍；B-PSG溶液组中药物的tl/2α、t_1/2β分别是马钱子碱溶液组中药物的1.5、1.7倍，AUC值是马钱子碱溶液组中药物的3.2倍，血浆清除率是马钱子碱溶液组的0.36倍。结论B-GPSG-NPs和B-PSG-NPs均改变了马钱子碱的药动学参数，且B-GPSG-NPs组效果更好，延长了药物在大鼠体内的半衰期和体内滞留时间，更有助于提高马钱子碱的生物利用度，发挥长效且高效的作用。更多还原

【Abstract】 Objective To compare the pharmacokinetics of glycyrrhetinic acid(GA)-mediated brucine self-assembled nanoparticles glycyrrhetinic acid-polyethylene glycol-dithiodipropionic acidmonostearate(B-GPSG-NPs), brucine and brucine self-assembled nanoparticles polyethylene glycoldithiodipropionic acid-monostearate(B-PSG-NPs). Methods An in vivo analytical method for the determination of brucine in the plasma was established by HPLC. Eighteen healthy rats, 9 males and 9females, were randomly divided into a nux vomica solution group, a B-GPSG-NPs solution group and a B-PSG-NPs solution group. The orbital blood was taken at different time points after tail vein injection,and the blood was collected at different time points after the administration. The fundus venous plexus capillary blood was taken at 10, 30, 60, 90, 120, 150, 180, 210, 240, 300, 420, and 600 min. After the content determination by HPLC, the drug time data fitting was conducted by DAS 2.0 software. The pharmacokinetic parameters were obtained, and the pharmacokinetics evaluated. Results The tl/2αand t1/2β in the B-GPSG-NPs solution group were 3.11, and 2.18 times higher than those in the brucine solution group, the AUC was 3.7 times higher than that in the brucine solution group, and the plasma clearance rate was 0.31 times higher than that in the brucine solution group. The tl/2α and t1/2β of the drugs in the B-PSG-NPs solution group were 1.5, and 1.7 times higher than that in the brucine solution group,the AUC was 3.2 times higher than that in the brucine solution group, and the plasma clearance rate was 0.36 times higher than that in the brucine solution group. Conclusion Both the B-GPSG-NPs and the B-PSG-NPs can change the metabolic kinetic parameters of brucine, and the effect of B-GPSG-NPs is better. Compared with the other two groups, B-GPSG-NPs prolongs the half-life and retention time of brucine in rats, and helps improve the bioavailability of brucine.更多还原